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Disrupted synaptic gene expression in Fabry disease: Findings from RNA sequencing
Laura López-Valverde1, María E Vázquez-Mosquera1, Cristóbal Colón-Mejeras1
1Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, RICORS-SAMID, CIBERER, University Clinical Hospital of Santiago de Compostela, Choupana s/n, 15706 Santiago de Compostela, A Coruña, Spain; Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, Choupana s/n, 15706 Santiago de Compostela, A Coruña, Spain.
Fabry disease (FD), a lysosomal storage disorder, involves synaptic dysfunction. RNA sequencing revealed altered gene expression in FD patients, suggesting lipid raft involvement in disease pathology.
Area of Science:
- Genetics
- Neuroscience
- Rare Diseases
Background:
- Fabry disease (FD) is an X-linked lysosomal storage disorder due to α-galactosidase A deficiency.
- Glycosphingolipid accumulation in FD causes progressive damage to kidneys, heart, and nervous system.
- Early diagnosis and understanding pathophysiology are crucial for managing FD.
Purpose of the Study:
- To identify gene expression patterns in FD patients using RNA sequencing.
- To investigate secondary cellular pathways affected by lysosomal dysfunction in FD.
- To explore the role of synaptic function and lipid rafts in FD pathogenesis.
Main Methods:
- International, multicenter, cross-sectional study.
- RNA sequencing (RNA-seq) analysis of blood samples from 50 FD patients and 50 controls.
- Functional enrichment analysis of differentially expressed genes.
Main Results:
- Over 400 differentially expressed genes identified, with 207 protein-coding genes, mostly overexpressed in FD.
- Functional analysis revealed significant alterations in synaptic function, including chemical synaptic transmission and membrane potential regulation.
- Key genes involved in voltage-gated ion channels, neurotransmitter receptors, and lipid raft-associated proteins were identified.
Conclusions:
- Lysosomal dysfunction in FD contributes to synaptic defects.
- Lipid rafts may play a role in the pathogenesis of FD.
- Further research into synaptic pathology is warranted for improved FD management.
